Glycan-Interacting Compounds and Methods of Use

Abstract

The present invention provides glycan-interacting antibodies and methods for producing glycan-interacting antibodies useful in the treatment and prevention of human disease, including cancer. Such glycan-interacting antibodies include humanized antibodies, derivatives and fragments thereof as well as related compositions and kits. Methods of using glycan-interacting antibodies for treatment and diagnosis are included.

1 .- 70 . (canceled) 
     
     
         71 . An isolated antibody that binds to sialyl(α2,6)N-acetylgalactosamine (STn), wherein the antibody comprises:
 a heavy chain variable domain (VH) comprising an amino acid sequence selected from SEQ ID NOs: 220-224, and a light chain variable domain (VL) comprising an amino acid sequence selected from SEQ ID NOs: 217-219. 
 
     
     
         72 . An isolated nucleic acid that encodes the antibody of  claim 71 . 
     
     
         73 . An isolated host cell comprising the isolated nucleic acid of  claim 72 . 
     
     
         74 . A method of producing an antibody that binds to sialyl(α2,6)N-acetylgalactosamine (STn), comprising culturing the host cell of  claim 73  under conditions suitable for expressing the antibody. 
     
     
         75 . A method of treating cancer comprising administering to a subject with cancer a therapeutically effective amount of the antibody of  claim 71 . 
     
     
         76 . A method of selecting a subject with cancer for treatment with an anti-STn antibody, comprising contacting a sample from the subject with the antibody of  claim 71 ; and detecting binding of the antibody to STn-expressing cancer cells. 
     
     
         77 . An antibody-drug conjugate comprising the antibody of  claim 71  conjugated to a therapeutic agent. 
     
     
         78 . The antibody-drug conjugate of  claim 77 , wherein said therapeutic agent is a cytotoxic agent. 
     
     
         79 . The antibody-drug conjugate of  claim 78 , wherein said cytotoxic agent is monomethyl auristatin E (MMAE) or monomethyl auristatin F (MMAF). 
     
     
         80 . A method of treating cancer comprising administering to a subject with cancer a therapeutically effective amount of the antibody-drug conjugate of  claim 77 . 
     
     
         81 . A method of killing a STn-expressing cell, comprising contacting the cell with an antibody-drug conjugate of  claim 77 . 
     
     
         82 . A method of making an antibody-drug conjugate, comprising contacting the antibody of  claim 71  with maleimidocaproyl-valine-citruline-p-aminobenzyloxycarbonyl-monomethyl auristatin E (MC-γc-PAB-MMAE).